A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3)

NCT04374136 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: AL001-3
• Study Type: interventional
• Target: 119
• Locations: 16 countries
• Sites: 44

Brief Summary

A phase 3 double blind, placebo controlled study evaluating the efficacy and safety of AL001 in participants at risk for or with frontotemporal dementia due to heterozygous mutations in the progranulin gene.

Conditions

Frontotemporal Dementia

Outcome Measures

Primary Outcomes (3)

• Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo as Measured by the CDR® Plus NACC FTLD-SB in Symptomatic Patients

  Part 1 Primary Endpoint - Change from baseline to Weeks 48, 72, and 96 in the CDR® plus NACC FTLD-SB. The Clinical Dementia Rating Dementia Staging Instrument PLUS National Alzheimer's Disease Coordinating Center frontotemporal lobar degeneration Behavior \& Language Domains Sum of Boxes (CDR® plus NACC FTLD-SB) is administered by a healthcare professional and based on individual ratings of the eight domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, personal care, language and behavior. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 8 individual domain ratings, or "box scores", were added together to give the CDR® plus NACC FTLD-SB which ranges from 0-24. Higher score indicates severe impairment.

  Through study completion, on average up to 96 weeks

• Part 1 Double Blind (Co-Primary US Endpoint) - Evaluation of the Treatment Effect of AL001 Compared With Placebo as Measured by Pharmacodynamic and Disease Pathology Biomarkers in Symptomatic Patients

  Geometric Mean Fold Change from baseline to Week 96 in PGRN concentrations in plasma

  Baseline to 96 weeks

• Part 2 OLE - To Assess the Long-term Safety and Tolerability of AL001 in Participants Who Have Completed Part 1 of the Study

  Part 2 OLE Primary Endpoint - Incidence, nature, and severity of AEs and SAEs in Part 2 OLE

  96 weeks

Secondary Outcomes (5)

• Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by CGI-S

  Baseline to 96 weeks

• Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by CGI-I

  Baseline to 96 weeks

• Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score

  Baseline to 96 weeks

• Part 1 Double Blind - Evaluation of the Safety and Tolerability of AL001 Compared With Placebo as Measured by Safety Assessments

  Baseline to 96 weeks

• Part 1 Double Blind: Clinical Progression as Measured by Frontotemporal Dementia Rating Scale (FRS) Logit Score in Symptomatic Participants

  baseline to 96 weeks

Study Arms (4)

Part 1 Blinded - AL001

EXPERIMENTAL

Participants receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period.

Drug: Part 1 Blinded - AL001

Part 1 Blinded - Placebo

PLACEBO COMPARATOR

Participants receive placebo administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period.

Drug: Part 1 Blinded - Placebo

Part 2 (OLE Treatment) - AL001

EXPERIMENTAL

Participants who received AL001 during the double-blind treatment period and enroll in the optional open-label extension receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks.

Drug: Part 2 (OLE Treatment) - AL001

Part 2 (OLE Treatment) - Placebo Switched to AL001

EXPERIMENTAL

Participants who received placebo during the double-blind treatment period and enroll in the optional open-label extension receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks.

Drug: Part 2 (OLE Treatment) - Placebo Switched to AL001

Interventions

Part 1 Blinded - AL001 DRUG

Administered via intravenous (IV) infusion

Part 1 Blinded - AL001

Part 1 Blinded - Placebo DRUG

Administered via intravenous (IV) infusion

Part 1 Blinded - Placebo

Part 2 (OLE Treatment) - AL001 DRUG

Administered via intravenous (IV) infusion

Part 2 (OLE Treatment) - AL001

Part 2 (OLE Treatment) - Placebo Switched to AL001 DRUG

Administered via intravenous (IV) infusion

Part 2 (OLE Treatment) - Placebo Switched to AL001

Eligibility Criteria

• Age: 25 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Persons with a progranulin gene mutation and at risk of developing FTD symptoms as evidenced by a biomarker, or persons with a progranulin gene mutation and diagnosed with FTD.
• If symptomatic, one or more of the criteria for the diagnosis of possible behavioral variant FTD, or a diagnosis of Primary Progressive Aphasia.
• Study partner who consents to study participation and who cares for/visits the participant daily for at least 5 hours per week.
• Written informed consent must be obtained and documented (from the participant or, where jurisdictions allow it, from their legal decision maker).

You may not qualify if:

• Dementia due to a condition other than FTD including, but not limited to, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, Huntington disease, or vascular dementia.
• Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
• Current uncontrolled hypertension, diabetes mellitus or thyroid disease. Clinically significant heart disease, liver disease or kidney disease. History or evidence of clinically significant brain disease other than FTD.
• Females who are pregnant or breastfeeding, or planning to conceive within the study period.
• Any experimental vaccine or gene therapy.
• History of cancer, unless in remission or stable/adequately controlled.
• Current use of anticoagulant medications (e.g., coumadin, heparinoids, apixaban).
• Residence in a skilled nursing facility, convalescent home, or long term care facility at screening; or requires continuous nursing care.

Sponsors & Collaborators

• Alector Inc.: lead
• GlaxoSmithKline: collaborator

Study Sites (44)

Dignity Health

Phoenix, Arizona, 85013, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Indiana University Health Neuroscience Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Alzheimer's Disease Center

Fairway, Kansas, 66205, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Mayo Comprehensive Cancer Center - PPDS

Rochester, Minnesota, 55905, United States

Location

Irving Institute for Clinical and Translational Research

New York, New York, 10032, United States

Location

University Of Cincinnati Gardner Neuroscience institute

Cincinnati, Ohio, 45219, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Houston Methodist Institute for Academic Medicine

Houston, Texas, 77030, United States

Location

Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia

Buenos Aires, C1428AQK, Argentina

Location

Box Hill Hospital

Box Hill, 3128, Australia

Location

The Queen Elizabeth Hospital

Woodville, 5011, Australia

Location

UZ Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

The University of Western Ontario

London, N6A 3K7, Canada

Location

Sunnybrook Research Institute - University of Toronto

Toronto, M4N 3M5, Canada

Location

CHU de Bordeaux

Bordeaux, 33404, France

Location

CHRU Lille

Lille, 59000, France

Location

Groupe Hospitalier Pitié Salpétrière

Paris, 75651, France

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

Universitätsklinikum Ulm

Ulm, 89075, Germany

Location

Eginitio University General Hospital of Athens - 1st University Neurology Clinic

Athens, Attica, 115 28, Greece

Location

University General Hospital of Alexandroupolis - Department of Neurology

Alexandroupoli, Evros, 68100, Greece

Location

Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara

Baggiovara, 41126, Italy

Location

ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia

Brescia, 25125, Italy

Location

IRCCS - Centro S. Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta

Milan, 20133, Italy

Location

PIA Fondazione Panico

Tricase, 73039, Italy

Location

Erasmus MC

Rotterdam, 3000 CA, Netherlands

Location

Centro Hospitalar do Porto - Hospital de Santo António

Porto, Porto District, 4099-001, Portugal

Location

Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, 3000-075, Portugal

Location

Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital CUF Descobertas

Lisbon, 1998-018, Portugal

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario de Donostia

Donostia / San Sebastian, 20014, Spain

Location

Karolinska Universitetssjukhuset Huddinge - PPDS

Huddinge, 141 57, Sweden

Location

Felix Platter Spital

Basel, 4055, Switzerland

Location

Istanbul University Medical Faculty

Istanbul, Fatih, 34093, Turkey (Türkiye)

Location

University College London

London, WC1E 6BT, United Kingdom

Location

MeSH Terms

Conditions

Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Alector Medical Information
• Organization: Alector

medinfo@alector.com

650-826-2454

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: May 5, 2020
• Study Start: July 23, 2020
• Primary Completion: September 1, 2025
• Study Completion: January 6, 2026
• Last Updated: September 21, 2026
• Results First Posted: September 21, 2026

Record last verified: 2026-08

Locations

IT (6); SE (1); AU (2); DE (2); GB (1); NL (1); PT (4); GR (2); CH (1); CA (2); US (14); BE (1); AR (1); ES (2); FR (3); TU (1)